This project will collect pilot data to explore the relationship between catechol-O-methyltransferase (COMT) Val158/108Met genotype and response to a 12-week computerized neurocognitive rehabilitation (CRT) given to chronic schizophrenic patients hospitalized at Manhattan Psychiatric Center, a 350-bed tertiary care psychiatric hospital. There is a broad consensus that cognitive deficits play a crucial role in both the pathogenesis and prognosis of schizophrenia. Effective treatment of cognitive impairments has the potential to improve overall illness outcome. Neurocognitive and functional neuroimaging studies have consistently revealed abnormalities in prefrontal cortex in patients with schizophrenia. The COMT gene is functionally expressed in neural systems considered important in a range of healthy brain functions and brain disorders, including schizophrenia. The COMT Met allele has been shown to be associated with a lower activity form of COMT, and with better performance on neurocognitive tests, while the COMT Val allele is associated with poorer executive cognition. This study will investigate the relationship of COMT polymorphism in patients with chronic schizophrenia with the response to CRT targeting visuospatial processing, attention, and cognitive flexibility. We hypothesize that the COMT Met allele will be associated with better neurocognitive performance after CRT, while the COMT Val allele will be associated with lesser gains in neurocognitive functioning in these areas. In addition, we will assess the genotype effect on different neurocognitive domains to characterize the neurocognitive phenotype more robustly related to the COMT polymorphism. The present proposal seeks to obtain funds to conduct the genotyping of the study sample, together with the proposed analysis. We are not requesting funds to conduct the CRT, nor for the neurocognitive evaluations and psychopathological assessments, which are provided by the hospital. After screening, 142 subjects will receive CRT for 3 hours per week for 12 weeks. Subjects will be evaluated on a standardized battery of neuropsychological assessments at baseline and at endpoint (Week 12). Patients having received CRT will provide saliva samples for genetic analysis. Genotyping will be conducted by psychiatric geneticist Dr. Herbert Lachman. Given the diversity and complexity of brain pathophysiology in schizophrenia, elucidating the possible relationship of COMT polymorphism with the level of performance in a neurocognitive rehabilitation treatment may be valuable for customizing cognitive treatments for patients. Given the diversity and complexity of brain pathophysiology in schizophrenia, elucidating the possible relationship of COMT polymorphism with the level of performance in a neurocognitive rehabilitation treatment may be valuable for customizing cognitive treatments for patients. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]